a study of cta101 ucar-t cell injection in patients with relapsed or refractory cd19+ b-line hematological malignancy

Conditions: Acute Lymphoblastic Leukemia; Non-hodgkin Lymphoma

Summary: a study of cta101 ucar-t cell injection in patients with relapsed or refractory cd19+ b-line hematological malignancy

this is a single arm, open-label, single-center study. this study is indicated for relapsed or refractory cd19+ b-line hematological malignancy: b-all and b-nhl. the selection of dose levels and the number of subjects are based on clinical tiral of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. primary objective is to explore the safety, main consideration is dose-related safety.

Eligibility criteria:
inclusion criteria: inclusion criteria applicable to all only: 1. male or female aged ≥ 3 and \<70 years old; 2. histologically confirmed diagnosis of cd19+ b-all per the us national comprehensive cancer network (nccn) clinical practice guidelines for acute lymphoblastic leukemia (2016.v1); 3. relapsed or refractory cd19+ b-all (meeting one of the following conditions): 1. cr not achieved after standardized chemotherapy; 2. cr achieved following the first induction, but cr duration is ≤ 12 months; 3. ineffective after first or multiple remedial treatments; 4. 2 or more recurrences; 4. the number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (morphology) and/or \>1% (flow cytometry); 5. philadelphia-chromosome-negative (ph-) patients; or philadelphia-chromosome-positive (ph+) patients who cannot tolerate tki treatments or do not respond to 2 tki treatments; inclusion criteria applicable to nhl only: 1. male or female aged ≥ 18 and \<70 years old; 2. histologically confirmed diagnosis per who classification criteria for lymphocytic tumors 2016, including dlbcl(nos), follicular lymphoma, chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms dlbcl, pmbcl and high grade b cell lymphoma; 3. relapsed or refractory dlbcl (meeting one of the following conditions): 1. no remission or recurrence after receiving second-line or above second-line chemotherapy; 2. primary drug resistance; 3. recurrence after autologous hematopoietic stem cell transplantation 4. according to lugano 2014, there should be at least one evaluable tumor lesion. applicable standards for all and nhl: 1. hla antibody(-) or hla antibody(+) and hla donor specific antibody(dsa)(-); 2. total bilirubin ≤ 51umol/l, alt and ast ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/l; 3. echocardiogram shows left ventricular ejection fraction (lvef) ≥ 50%; 4. no active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%; 5. estimated survival time ≥ 3 months; 6. ecog performance status 0 to 2; 7. patients or their legal guardians volunteer to participate in the study and sign the informed consent. exclusion criteria: 1. patients with extramedullary lesions, except those with cnsl (cns-1) under effective control (for all patients only); 2. confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, burkitt's leukemia/lymphoma per who classification criteria (for all patients only); 3. patients with hereditary syndrome such as fanconi anemia, kostmann syndrome, shwachman syndrome or any other known bone marrow failure syndrome (for all patients only); 4. patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by mri) (for nhl patients only) ; 5. extensive involvement of gastrointestinal lymphoma (for nhl patients only); 6. radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening; 7. have a history of allergy to any of the components in the cell products; 8. prior treatment with any car t cell product or other genetically-modified t cell therapies; 9. according to the new york heart association (nyha) cardiac function classification criteria, subjects with grade iii or iv cardiac insufficiency; 10. myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment; 11. severe primary or secondary hypertension of grade 3 or above (who hypertension guidelines, 1999); 12. electrocardiogram shows prolonged qt interval, severe heart diseases such as severe arrhythmia in the past; 13. history of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; 14. patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis). 15. indwelling catheters in vivo (e.g. percutaneous nephrostomy, foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). ommaya storage, dedicated central venous access catheters such as port-a-cath or hickman catheters are allowed; 16. history of other primary cancer, except for the following conditions: 1. cured non-melanoma after resection, such as basal cell carcinoma of the skin; 2. cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment; 17. patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy; 18. patients with graft-versus-host disease (gvhd); 19. prior immunizations with live vaccine 4 weeks prior to screening; 20. history of alcoholism, drug abuse or mental illness; 21. if hbsag positive at screening, hbv dna copy number detected by pcr in patients with active hepatitis b \> 1000 (if hbv dna copy number≤1000, routine antiviral therapy is required after enrollment), as well as cmv, hepatitis c, syphilis infection; 22. concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids; 23. patients who have participated in any other clinical studies within 2 weeks prior to screening; 24. pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender); 25. any situations that the investigator believes may increase the risk of patients or interfere with the results of study.